Outcome of ABCA4 microarray screening in routine clinical practice

Molecular vision

Klevering, B. Jeroen¹  Ernest, Paul J.G.¹  Hoyng, Carel B.¹  Boon, Camiel J.F.¹  Hoefsloot, Lies H.¹ 

DOI  :  

学科分类：生物化学/生物物理

来源: Molecular Vision

【 摘 要 】

Purpose: To retrospectively analyze theclinical characteristics of patients who were screened for mutationswith the ATP-binding cassette transporter gene ABCA4 (ABCA4)microarray in a routine clinical DNA diagnostics setting. Methods: We performed a retrospectiveanalysis of the medical charts of 65 patients who underwent an ABCA4microarray screening between the years 2002 and 2006. An additionaldenaturing gradient gel electrophoresis (DGGE) was performed in thesepatients if less than two mutations were found with the microarray. Weincluded all patients who were suspected of autosomal recessiveStargardt disease (STGD1), autosomal recessive cone–rod dystrophy(arCRD), or autosomal recessive retinitis pigmentosa at the time ofmicroarray request. After a retrospective analysis of the clinicalcharacteristics, the patients who were suspected of STGD1 werecategorized as having either a typical or atypical form of STGD1,according to the age at onset, fundus appearance, fluoresceinangiography, and electroretinography. The occurrence of typicalclinical features for STGD1 was compared between patients withdifferent numbers of discovered mutations. Results: Of the 44 patients who weresuspected of STGD1, 26 patients (59%) had sufficient data available fora classification in either typical (six patients; 23%) or atypical (20patients; 77%) STGD1. In the suspected STGD1 group, 59% of all expectedpathogenic alleles were found with the ABCA4 microarray. DGGEled to the finding of 12 more mutations, resulting in an overalldetection rate of 73%. Thirty-one percent of patients with two or threediscovered ABCA4 mutations met all typical STGD1 criteria. Anage at onset younger than 25 years and a dark choroid on fluoresceinangiography were the most predictive clinical features to find ABCA4mutations in patients suspected of STGD1. In 18 patients suspected ofarCRD, microarray screening detected 22% of the possible pathogenicalleles. Conclusions: In addition to confirmationof the diagnosis in typical STGD1, ABCA4 microarray screeningis usually requested in daily clinical practice to strengthen thediagnosis when the disease is atypical. This study supports the viewthat the efficiency and accuracy of ABCA4 microarray screeningare directly dependent upon the clinical features of the patients whoare screened.

【 授权许可】

Unknown